ABSTRACT

Background
The benefit of anthracyclines for patients with high 21-gene recurrence score (RS) is unclear, despite the
widespread use of RS to guide adjuvant chemotherapy treatment for hormone receptor-positive
(HR+)/HER2-negative (HER2-) breast cancer. This study aimed to assess whether patients with RS > 31 would have improved outcomes with the addition of anthracyclines to taxane-based chemotherapy.

Patients and Methods
We included patients from TAILORx with RS ≥ 11 who received treatment with either taxanes with
cyclophosphamide (TC) or taxane with anthracyclines/cyclophosphamide (T-AC). Distant recurrence-free interval (DRFI), distant recurrence-free survival (DRFS), overall survival (OS) were compared, controlling for age, tumor size and grade, receptor status, and RS. Spline regression was used to estimate adjusted hazard ratio (aHR) for receipt of T-AC (vs TC) for these endpoints as a function of RS.

Results
A total of 2,549 patients who received either T-AC or TC were included in the primary analysis. In patients with RS > 31, receipt of T-AC was associated with improved DRFI (5-year rate of 96.1% with T-AC vs 91.0% with TC; aHR, 0.31; P = 0.006), DRFS (95.4% vs 89.8%; aHR, 0.49; P = 0.032), and a trend towards improved OS (adjusted 5-year rate 97.3% vs 93.6%; aHR, 0.67; P = 0.31). Spline regression demonstrated increasing anthracycline benefit with increasing RS.

Conclusion
Patients with early-stage, HR+/HER2- breast cancer with the highest genomic risk disease (RS > 31) may benefit from the addition of an anthracycline to taxane-based adjuvant chemotherapy. Genomic RS testing may predict anthracycline benefit more accurately than clinicopathologic factors such as nodal status.

Keywords: breast cancer, HR+/HER2-negative, recurrence score, anthracyclines